POS1321 FEATURES OF MACROPHAGE ACTIVATION SYNDROME IN SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS IN THE ERA OF BIOLOGIC THERAPY
Authors: I. Kriulin, E. Alexeeva, T. Dvoryakovskaya, R. Denisova, K. Isaeva, A. Chomakhidze, A. Mamutova, O. Lomakina, A. Fetisova, M. Gautier, K. Chibisova, E. Krekhova, I. Tsulukiya
Journal: Annals of the Rheumatic Diseases (2022)

Background Macrophage activation syndrome (MAS) is a severe hyperinflammatory response that develops against the background of juvenile idiopathic arthritis (JIA). It is known that the clinical feature of MAS on biologic therapy has other clinical manifestations, different from biologically naive patients. Objectives To study the clinical and laboratory features of macrophage activation syndrome in patients with juvenile idiopathic arthritis with systemic onset (sJIA) on the biologic therapy. Methods The study included 100 patients with MAS (114 cases of MAS) who observed in the rheumatological department of the National Medical Research Center for Children’s health of Ministry of health. All patients met the criteria for the diagnosis of sJIA and MAS. There were children in our study who did not receive biologic therapy – 84 (74%) cases, and children who had MAS in the biologic therapy – 30 cases (26%). The drugs are distributed as follows: tocilizumab - 7 cases (6%), kanakinumab - 20 cases (17%), etanercept – 2 cases (2%), adalimumab – 1 case (1%). For pairwise intergroup comparisons of quantitative variables, the nonparametric Mann-Whitney test was used. Results In comparative analysis of biologic-naive and on biologic patients, the greatest differences were obtained for the following clinical manifestations: rash, lymphadenopathy, myalgia (p&lt;0.05). Fever was the most common symptom in both groups and was present in almost all patients (99%). All patients had elevated level of ferritin in the blood serum (773 ng/ml to 130149 ng/ml). Laboratory picture of MAS in the group of on biologic patients differed significantly from the group of patients naive for biologic therapy (Table 1). The most significant differences were found among the following laboratory parameters: hemoglobin level, the number of erythrocytes and platelets, erythrocyte sedimentation rate (ESR), levels of C-raective protein (CRP), ferritin, lactatedehydrogenase (LDH), albumin. Table 1. Laboratory data of patients with MAS. n Reference values Median Minimum Maximum Mann-Whitney Criterion (p) Biologic-naive cases of MAS(n= 84) Hemoglobin, g/l 84 120-145 96,50 61,00 145,00 0,008 Red blood cells, 10 12 /l 84 4,5-5,3 3,78 2,13 5,01 0,001 Platelets, 10 9 /l 84 150-440 149,00 41,00 523,00 0,025 White blood cells, 10 9 /l 84 4,5-11,5 4,42 0,69 25,84 0,074 ESR, mm/h 84 2-20 45,00 2,00 111,00 0,001 CRP, mg/l 84 0-5 111,56 7,54 368,31 0,006 Ferritin, ng/ml 84 14-124 4195,21 702,38 130149,20 0,022 LDH, U/l 84 91-295 413,50 162,00 5245,00 0,059 Albumin, g/l 84 38-54 29,00 16,10 63,00 0,001 On biologic cases of MAS(n = 30) Hemoglobin, g/l 30 120-145 104,50 67,00 163,00 0,008 Red blood cells, 10 12 /l 30 4,5-5,3 4,17 3,10 6,15 0,001 Platelets, 10 9 /l 30 150-440 101,50 4,00 362,00 0,025 White blood cells, 10 9 /l 30 4,5-11,5 3,22 0,70 15,58 0,074 ESR, mm/h 30 2-20 17,50 2,00 98,00 0,001 CRP, mg/l 30 0-5 55,77 1,86 407,12 0,006 Ferritin, ng/ml 30 14-124 2319,59 773,90 121396,00 0,022 LDH, U/l 30 91-295 600,00 10,60 2148,57 0,059 Albumin, g/l 30 38-54 32,80 20,30 51,90 0,001 Conclusion On biologic patients may also develop MAS, which is often difficult to diagnose due to the poor clinical picture and low laboratory activity. In this case, hyperferritinemia remains as a highly specific marker of MAS. References [1]Crayne CB, Albeituni S, Nichols KE, Cron RQ. The Immunology of Macrophage Activation Syndrome. Front Immunol. 2019 Feb 1;10:119. doi: 10.3389/fimmu.2019.00119. PMID: 30774631; PMCID: PMC6367262. [2]Henderson LA, Cron RQ. Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Childhood Inflammatory Disorders: Diagnosis and Management. Paediatr Drugs. 2020 Feb;22(1):29-44. doi:10.1007/s40272-019-00367-1. PMID: 31732958; PMCID: PMC7334831. [3]Ravelli A, Davì S, Minoia F, Martini A, Cron RQ. Macrophage Activation Syndrome. Hematol Oncol Clin North Am. 2015 Oct;29(5):927-41. doi:10.1016/j.hoc.2015.06.010. Epub 2015 Aug 25 PMID: 26461152 Disclosure of Interests Ivan Kriulin Speakers bureau: Speaker for Novartis., Ekaterina Alexeeva Speakers bureau: Speaker for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis., Tatyana Dvoryakovskaya Speakers bureau: Speaker for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis., Rina Denisova Speakers bureau: Speaker for Roche, AbbVie, MSD, Novartis., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Sanofi and Novartis., Ksenia Isaeva Grant/research support from: Financial grants from Roche, Novartis and Sanofi., Aleksandra Chomakhidze: None declared, Anna Mamutova Speakers bureau: Speaker for Novartis., Grant/research support from: Financial grants from Eli Lilly., Olga Lomakina Grant/research support from: Financial grants from Pfizer, Eli Lilly., Anna Fetisova Grant/research support from: Financial grants from Amgen., Marina Gautier: None declared, Kristina Chibisova: None declared, Elizaveta Krekhova Speakers bureau: Speaker for Novartis., Irina Tsulukiya: None declared